Body fluid sampling device

ABSTRACT

Body fluid sampling device comprising a skin-piercing element having a collection zone for receiving body fluid. In one embodiment, the collection zone includes a plurality of holes, e.g., 3 or more holes, or 50 to 100 holes. The hole size may be small, e.g., having a diameter of 0.01 to 0.5 mm. The holes may or may not extend through the lancet. In some embodiments, the holes have a depth of 50 to 500 μm. In other embodiments, the collection zone is porous, or is a roughened area. The collection zone can take up a very small volume of body fluid, e.g., 3 to 10 nL, in a very short time period, e.g., less than 0.5 seconds. In other embodiments, the device further comprises a fluid receiving means spaced apart from the collection zone so that body fluid in the collection zone will not contact the fluid receiving means initially.

REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.11/470,368 filed Sep. 6, 2006, which is a continuation of InternationalApplication No. PCT/EP2005/002357 filed Mar. 7, 2005, which claims thebenefit of U.S. Provisional Application No. 60/642,956, filed Jan. 11,2005 and European Patent Application No. EP 04005385.2, filed Mar. 6,2004, which are all hereby incorporated by reference in theirentireties.

BACKGROUND

The present invention relates to the field of body fluid analysis inorder to monitor the concentration of analytes such as blood glucoseconcentration.

The invention concerns a device and system for sampling small amounts ofbody fluid. A body fluid sampling device comprises a skin-piercingelement with a collection zone (e.g. a fluid pathway) for receiving bodyfluid therein. At least a portion of the collection zone is open to theenvironment so that fluid can be sampled. The sampling device or aseparate element comprises a fluid receiving means which is out offluidic contact with the collection zone of the skin-piercing element sothat sampled fluid in the collection zone will not contact the fluidreceiving means initially. The body fluid sampling device with connectedcollection zone or a system comprising a body fluid sampling device andfluid receiving means can be brought into a second state in which atleast a portion of the collection zone contacts the fluid receivingmeans so that fluid is transferred. Based on signals from a test zone ofthe fluid receiving means analyte concentration can be determined.

Systems for sampling body fluids are already known in the prior art inwhich body fluid is taken up into a disposable element. Blood collectionand analytical systems are known from document EP 0 199 484 for examplewhich comprises a disposable unit with a capillary to collect body fluidand to transport the body fluid into a detection area. The furtherdevelopment of this concept is described in WO 97/42888. The arrangementdescribed in this document is particularly suitable for collectingrelatively small amounts of body fluids which is primarily accomplishedby pressing a ring onto the area surrounding a collection site andapplying a pump movement. A system for analysis based on small amountsof interstitial fluid is known from EP 0 723 418. For this purpose avery thin hollow needle is inserted into the dermis and interstitialfluid is conveyed through the needle to a test zone by applying pressureto the area surrounding the puncture site. A highly miniaturizedarrangement which also utilizes a hollow needle to withdraw body fluidis known from U.S. Pat. No. 5,801,057. A particular advantage of thisarrangement is the extremely thin needle which can be inserted into thearm region of a patient essentially without any pain.

Whereas the arrangement described in U.S. Pat. No. 5,801,057 alreadyfulfils numerous practical requirements, some features are in need ofimprovement. A general problem with the sampling devices according tothe previously mentioned document is to manufacture the hollow needlecost-effectively and as small as possible.

With this aim body fluid samplers which have an open collection zonehave been contemplated. US 2003/0018282 and US 2003/0028125 bothdescribe skin-piercing devices which have an open channel for body fluidsampling which at least partially is located in a region of a piercingneedle. Body fluid sampled into the collection zone is transferred to atesting zone which is fixed to the skin-piercing element. In particularUS 2003/0028125 describes that the skin-piercing element is integralwith a part of a test strip. A further document that contemplates asimilar sampling and testing device providing a pooling area isdescribed in US 2002/0168290.

WO 01/72220 describes a fluid sampling and analysis device with a dermalpenetration probe. Said penetration probe being in direct fluidcommunication with an analysis chamber. Accordingly this device designhas the disadvantage that sterilization of the penetration probe whichis regularly achieved by gamma radiation destroys the test chemistrylocated in the analysis chamber. Further sampling and analysis arespatially fixed to one another and therefore need to be close togetherto allow efficient sample transfer.

SUMMARY

The prior art sampling and testing devices describe embodiments wheresample from a capillary channel is directly transferred to a testingzone which is in fluidic contact with the channel. Contrary to that thepresent invention proposes body fluid sampling and testing devices wherethe collection zone in a phase in which sample is taken up is out offluidic contact with a testing zone. In a second phase, after havingtaken up a fluid sample into the collection zone, at least a portion ofthe collection zone is being transferred in a second position in whichat least a portion of the collection zone comes into contact with afluid receiving means that receives fluid from the collection zone.Alternatively the fluid receiving means can be moved or both, the fluidreceiving means as well as the collection zone may be moved.

In a first preferred embodiment a body fluid sampling device comprises askin-piercing element having a collection zone for receiving body fluidand a fluid receiving means comprising a test zone. Said fluid receivingmeans being out of fluidic contact with said collection zone so thatfluid present in said collection zone will not contact the fluidreceiving means. Alternatively the fluid receiving means may not have anintegrated test zone but it is contacted with a separate test zone toachieve analytical testing.

A second preferred embodiment comprises an integrated device with askin-piercing means having a fluid collection zone as well as a fluidreceiving means with a test zone. Said integrated device being adaptedto undergo a physical change (in particular a movement of the collectionzone relative to the fluid receiving means) upon actuation so as toassume a contacting state in which a fluid in said collection zonecontacts said fluid receiving means.

A third preferred embodiment concerns a device according to the firstpreferred embodiment, wherein said device has a moveable portion whichcan be moved and at least a portion of said fluid collection zone or ofsaid fluid receiving means is located on said moveable portion.

A fourth preferred embodiment concerns a device according to the firstpreferred embodiment, wherein body fluid received in said collectionzone is moved by electrical actuation onto the fluid receiving means.

A fifth preferred embodiment comprises a device according to the firstpreferred embodiment, wherein body fluid received in said collectionzone is transferred into contact with the fluid receiving means withoutusing body fluid as transport means.

According to a sixth preferred embodiment of the invention the bodyfluid sampling device is contacted with a separate transport element toreceive fluid which then in turn is contacted with a test zone on aseparate element.

The present invention in particular is useful for handheld testingsystems.

Further it is preferred if the skin-piercing element is a disposablethat it is only used once. It is also preferred to employ disposablefluid receiving means which are only used once.

According to an embodiment of the prior art the transport meanscomprises e.g. a capillary reaching from the collection zone to thefluid receiving means (e.g. EP 1 360 931). The body fluid is taken up atthe test zone and is transferred to contact the fluid receiving means bycapillary actuation, i.e. the subsequently picked up body fluid pushesthe sample to the fluid receiving means. This additionally needed fluidvolume, the so-called dead volume, serves as transport means to transferthe fluid used for the analysis to contact the fluid receiving means.This means that by principle more body fluid volume has to be collectedthan is needed for the measurement and this dead volume increases withincreasing transfer distance. According to the present inventioncontrary to the prior art there is no dead volume needed. Ideally thewhole sample volume that is collected in the collection zone istransferred to the fluid receiving means to be used for the measurement.Of course, it is likely that some sample remains in the collection zone,as it is the case by using a capillary. Furthermore, according to thepresent invention the body fluid volume needed to be sampled formeasurement does not necessarily increase with increasing distancebetween collection zone and fluid receiving means.

Another advantage of the invention is, that due to the fact thatskin-piercing element and fluid receiving means initially are not influidic contact, they can easily be separated in two parts. Theskin-piercing element, or at least part of it, punctures the skin andtherefore needs to be sterilized. Test zones, in the most cases however,are sensitive to sterilization. Separating skin-piercing element andfluid receiving means into two parts solves this problem as the skinpiercing element can be sterilized separately from the fluid receivingmeans an thus avoiding a destruction of the test chemistry.

The fluid receiving means may itself contain a test zone or it may be anelement without a test zone that transports sample to a separate testzone. In both cases wetting of the test zone, however, can be initiatedin a controlled manner by the contacting step. This triggering of testzone wetting has the advantage that the reaction time (i.e. the timebetween contacting a test chemistry with sample fluid and reading oftest results) can be controlled which leads to higher accuracy ofanalyte determination.

A further advantage compared to the prior art sampling devices is thatfluid sampling and contacting of the sampling device with a testing zonecan be conducted at different locations. Fluid sampling for example canbe done at the front end of a hand-held apparatus while contacting witha testing zone can be made within the apparatus. Due to this shuttlefunction of the skin-piercing element optics or other evaluation meanscan be moved into the interior of a housing which is advantageous withview to the limited space at the front end. Furthermore a physicalseparation of the test zone from blood during the sampling step avoidsthat test chemistry diffuses into the human body during sampling. Thepresent invention therefore has significant advantages over the fluidsampling devices of the prior art.

One particular field of application of systems and devices forwithdrawing small amounts of body fluid is the so-called spot monitoringin which the concentration of particular analytes present in body fluidsis determined at a particular time. Such measurements can be carried outrepeatedly at time intervals in order to monitor a change of analyteconcentration. Such analysis employing disposable test elements hasproven to be particularly advantageous especially in the field of bloodsugar measurement by diabetics. If excessively high blood sugar values(hyperglycaemia) occur in a diabetic over a period of time, this canlead to serious long-term damage such as blindness and gangrene. If, onthe other hand, a diabetic gets into a state of hypoglycaemia because hehas for example injected too large a dose of insulin, this can becomelife-threatening if the diabetic falls into a so-called hypoglycaemicshock. A regular control of the blood sugar level enables the diabeticto avoid hyperglycaemic and hypoglycaemic states and also to learn howto coordinate his eating habits, bodily activity and insulin medication.In addition to improving and maintaining the health of diabetics,regular blood sugar monitoring also has considerable overall economicadvantages since high costs for secondary diseases can be avoided. Thereasons which prevent a more widespread and consequent use of bloodsugar monitoring are primarily the pain caused by the required bodyfluid collection and the multiple handling steps of systems currently inthe market. With the currently used systems the diabetic or medicalstaff must firstly obtain a drop of blood which is usually obtained fromthe finger pad. So-called lancing devices may be used to reduce pain. Alancing device must be firstly loaded with a lancet, tensioned, placedon the body surface and triggered. After the lancing process the userhas to milk his finger in order to convey a drop of blood out of thepuncture wound. Before this procedure the diabetic has to already placea test strip in a blood sugar measuring instrument and activate it. Thedrop of blood can now be applied to the test strip and after, forexample, 10 s, a blood sugar measurement is available. Finally the userhas to dispose of the spent lancet and test strip. The present inventionenables the process of blood sugar measurement to be greatly simplified.

The present invention, however, can be employed for other analytes aswell. Further it is possible to analyse sampled fluid with differenttest zones simultaneously or subsequently.

Simplification of testing according to the present invention not only isadvantageous for current users, it hopefully also has the effect thatmore people having diabetes or other diseases will test their bloodglucose concentration or other parameters on a more regular basis.

A sampling device and system according to the present invention servesto withdraw small amounts of body fluid. Preferably, the body fluidsample is received in the collection zone while the collection zone isin the body, i.e. no blood needs to leak from the puncture site and theuser does not need to milk his finger and to move the drop of blood onhis finger to a test zone. Of course, it is also possible to use bloodthat leaks from the puncture site. In this context body fluids areunderstood in particular as blood, interstitial fluid and mixtures ofthese body fluids. Whereas conventional blood collection systems usuallycarried out sampling on the finger pad, the collection system accordingto the present invention can also be used to withdraw blood fromalternative sites on the body such as the forearm and the palm.

A skin-piercing element for withdrawing small amounts of body fluidaccording to the present invention has a protruding portion with asharpened end for piercing skin. Within at least a region of theprotruding portion a collection zone is located which has the ability tocollect body fluid. This in particular can be achieved by a capillaryactivity. At least a part of the body fluid receiving structure is open.A capillary structure is understood within the scope of the invention asa body which transports body fluid as a result of capillary forces. Incase of a capillary channel fluid is transported towards the proximalend of the skin-piercing element when the distal area is contacted withbody fluid. With regard to this embodiment the capillary structureaccording to the invention is similar to the open needle structuresdescribed in US 2003/0018282 and US 2003/0028125 to which reference ismade herewith. However, an important difference is that these documentsdescribe microneedles where the capillary channel is in fluidic contactwith a test zone so that body fluid received in the capillary channel isdirectly applied to the test zone and hence initiates reaction.

Capillary structures in the collection zone may be manufactured byphotolithographic methods like those described in the document U.S. Pat.No. 5,801,057 and which are known from the field of semiconductortechnology. It is also possible to provide channels, grooves, holes etc.which are open to the outside in solid needles by milling, etching andsuch like. Such structures are preferably generated by etching processesas photochemical milling (PCM). PCM is based on optical pattern transferand etch processes. It is known to be a micromachining technology.

In addition to the already mentioned methods for incorporating capillarystructures into surfaces, it is also possible to generate the capillarychannels by assembling bodies in a way that capillary gaps are created.Thus it is for example possible to fasten two or more solid needlestogether for example by welding such that the contact areas of the solidneedles form capillary channels. In a corresponding manner it is alsopossible to twist wires or fibres together in the form of a strandedwire such that numerous contact areas are formed which generate thecapillary channels. The wires or fibres might be made of metal, glass orcarbon, and can be solid or hollow, for example it can be necessary togrind a lancet surface to achieve open capillaries. It is also possiblethat the capillary is not open to the environment for the whole time,e.g. it may be opened only during the skin-piercing step to collect thebody fluid. Further skin-piercing elements with fluid pathways can becreated by applying one or more layer of materials (e.g. laminatedfoils) onto a flat needle in a way that a capillary gap is createdbetween the layers or is provided in one such layer.

The capillary structures according to the present invention are,however, not restricted to capillary channels leading from a distal to aproximal end of the skin-piercing element. Also porous structures orholes may be employed to sample fluid. With the present invention it isnot essential that capillaries transport fluid over a macroscopicdistance to achieve wetting of a test zone. Instead the collection zoneand fluid receiving means are moved into proximity.

To achieve proper sampling of body fluid into the channel of theskin-piercing element and to enhance sampling speed it is preferred toemploy hydrophilic materials, particularly for the collection zone.Alternatively or in addition to hydrophilic materials, hydrophiliccoatings may be employed.

The skin-piercing devices are introduced into the skin and thereforehave to be sterile to avoid infections and inflammations. According tothis the skin-piercing elements may be packaged in a sterile way e.g. ina blister. In a preferred embodiment the tips of skin-piercing elementsare covered by e.g. a plastic to avoid contamination after theskin-piercing elements are sterilized (e.g. by gamma-radiation).Particularly preferred are tip protections as described in WO 01/66010.Such tip protection covers which surround the needle can be producedeasily and also can be removed easily so that an automatic removalwithin a system becomes feasible. A system for analysis according to thepresent invention may comprise an actuator to pull off a cap from thetip before skin-piercing is initiated. Alternatively the skin piercingelement may be transferred into a position where the protective cap isheld (e.g. by form-fit) and is removed from the skin-piercing element bymoving the skin-piercing element away from the fixed cap. Preferablythis movement can be conducted by a lancing drive or transport meanswhich is employed anyhow.

Even embodiments are possible where the protective cap is pierced by thelancing tip of the skin-piercing element as e.g. shown in FIG. 1 or 6 ofWO 0166010.

Alternatively it is possible to sterilize the skin-piercing elementwithin the handheld device directly before use by e.g. ultravioletradiation or heat.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows a body fluid sampling device according to one embodiment.

FIG. 2 shows a body fluid sampling device according to anotherembodiment.

FIG. 3 shows a body fluid sampling device according to still yet anotherembodiment.

FIG. 4 shows an example of a hollow lancet comprising three elongatedholes.

FIG. 5 shows the concept of electrical triggering a contact of samplefluid with a test zone.

FIG. 6 shows a finger cone used to improve sample collection.

FIG. 7 shows an embodiment in which lancets and test strips are arrangedin a drum magazine.

FIGS. 8, 9, 10, and 11 show various cross-sectional views of the FIG. 7magazine during lancing and fluid collection.

FIG. 12 shows a skin piercing element according to another embodimentthat includes a round, solid lancet with a groove or recess to form acollection zone.

FIG. 13 shows a skin-piercing element according to still yet anotherembodiment.

FIG. 14 shows the FIG. 13 skin-piercing element together with a fluidreceiving means including a test zone.

FIG. 15 shows a body fluid testing device that contains a plurality oftest zones located on a test media cassette.

FIG. 16 shows an embodiment where a skin-piercing element that includesa collection zone and a fluid receiving means connected via a hinge.

FIG. 17 shows a further embodiment to transfer a sample from a skinpiercing element onto a test zone.

FIG. 18 shows a skin-piercing element having two parts which can bemoved relative to one another.

FIG. 19 shows an array of sealed fluid receiving which are sealedagainst the environment by a sealing foil.

DESCRIPTION OF SELECTED EMBODIMENTS

For the purpose of promoting an understanding of the principles of theinvention, reference will now be made to the embodiments illustrated inthe drawings and specific language will be used to describe the same. Itwill nevertheless be understood that no limitation of the scope of theinvention is thereby intended. Any alterations and further modificationsin the described embodiments, and any further applications of theprinciples of the invention as described herein are contemplated aswould normally occur to one skilled in the art to which the inventionrelates.

A preferred embodiment is described in FIG. 1. A body fluid samplingdevice according to one aspect the invention is shown, wherein thecollection zone comprises holes or a porous surface in or on which thereceived body fluid is collected. It is preferred that the samplingdevice has 3 or more holes for receiving sample or even much more incase of porous surfaces. The depicted skin-piercing element is a flatlancet (1), e.g. made of stainless steel, silicon or a plastic carrierfilm with a thickness of 0.05 to 1 mm, preferably 0.2 mm, having smallholes (2) near the piercing edges (3) of the lancet. The holes (2) maybe through holes or blind holes, and may have a diameter of preferably0.01 to 0.5 mm. The number of holes may vary from a few holes to a fewhundred holes, preferred are 3 or more holes, even more preferred are 50to 100 holes. A preferred diameter is around 20 μm. Alternatively theskin-piercing element may be a round solid (4) or hollow (5) lancethaving sharpened surfaces with edges for piercing as shown in FIG. 2.Round lancets typically comprise three surfaces (6-8). Preferably around, solid lancet may have the collection zone at its third surface(8). FIG. 2, for example, displays a collection zone (9) comprising 70through holes (2) of 20 μm in diameter, FIG. 3 describes 7 blind holes(2) with a diameter of 0.15 mm and a depth of 80 μm. FIG. 4 shows anexample of a hollow lancet (5) comprising three elongated through holes(2) in the range of 0.15 mm to 0.35 mm.

Further embodiments for a porous surface to collect the body fluid areroughened areas on one of the surfaces of the skin-piercing element,e.g. made by grinding. The grinding recesses form a repository tocollect the body fluid. Alternatively pores may be applied to form thecollection zone. These can be achieved e.g. by a porous coating or byselective etching of the lancet material, e.g. a special alloy of aresistant and a solvent metal, creating a spongy surface. Especiallywhen using flat lancets thin fibers of a second material may beincorporated into the surface, e.g. by rolling, that can be selectivelyetched.

According to the above embodiments it is possible that the direction offlow of fluid into the collection zone and out of it into a fluidreceiving means is the same (e.g. in case of through holes the fluidreceiving means is contacted with the side of the holes opposing thesample entrance) or the direction of flow may be reversed (fluidreceiving means is contacted with the opening or holes into which sampleis received).

As already stated above it is advantageous that the capillary channelsare open to the outside such that they can take up body fluid while thecapillary structure is inserted into the body.

The shape of the skin-piercing element is relatively uncritical. It canfor example be in the form of a small cube. Special measures are usuallynot necessary to mount the skin-piercing element in a drive unit but aholding region located at the proximal end of the skin-piercing elementis preferred. Advantageously the holding area is formed integral withthe other regions of the skin-piercing element. Piercing element designscan be employed that are known for disposable lancets of conventionalblood sampling systems. For example the holding region can have tapersinto which spring elements of a holder of a drive unit engage in orderto hold the piercing element. The piercing element is advantageouslypositioned within a holder in such a manner (for example by pressing theend of the piercing element facing away from the tip against a stop)that it allows a good control of the piercing depth. Reference is madeto the document EP B 0 565 970 with regard to such a holder and theinteraction between the holder and the disposable lancing unit.

A body fluid sampling device in addition to the skin-piercing elementhas a fluid receiving means which is spatially separated from thecollection zone of the skin-piercing element in a way so that fluid in afluid collection zone of the skin-piercing element will not contact thefluid receiving means during filling. The fluid receiving means and thecollection zone, however, are contacted to each other after fluid samplehas been received in at least a part of the collection zone and whenstart of the analytical reaction is desired. Such contacting primarilyis a mechanical act where the channel holding the sample fluid and thefluid receiving means are moved together. This contacting includespressing the fluid collection zone and fluid receiving means together ormay mean a wiping movement.

Separation of skin-piercing element and fluid receiving means enablesembodiments where the skin-piercing element is employed as a shuttle totransport sampled fluid to a fluid receiving means. This is particularlyadvantageous when fluid sampling is made in a spatially restricted area(e.g. the front end of apparatus) and the fluid receiving means does notfit well into this limited space. The latter in particular is the casefor fluid receiving means fixed to a tape as, for example, described inEP 0 202 6242.4, U.S. Pat. No. 4,218,421 and EP 0 299 517. The shuttlefunction enables a testing process with the steps of

-   -   pricking skin with the skin-piercing element    -   receiving body fluid in a collection zone of the skin-piercing        element    -   contacting a portion of the collection zone with a fluid        receiving means to provide a test zone with sample fluid    -   detecting a change of the test zone which relates to the        concentration of an analyte.

In a preferred embodiment the transport means for transporting orshuttling and contacting the sampled body fluid with the fluid receivingmeans is done automatically. Preferred are but not restrictingembodiments for automatic transfer are electrical, mechanical actuation,actuation by spring forces, manual actuation, e.g. by a user, pushing aslider, or a combination of these actuation principles. Particularlyelectrical motors may be employed to achieve the contacting.

The mentioned transport means can be controlled by a control unit whichcontrols movement of the transport means including a spatial control aswell as a timely control. By this the time for filling the samplingelement, the timecourse of transportation, the time for contacting witha fluid receiving means and the time when the test zone is evaluated canbe controlled. Such control improves fluid sampling and testing andtherefore increases reliability.

Further a control unit in cooperation with a transport means can beemployed to improve the sampling step. Particularly it is possible towithdraw the skin-piercing element only partially having it remaining inthe skin but the lancing channel is already opened so that body fluidcan emerge more easily and is taken up by the collection zone. It iseven possible to rotate or move the skin-piercing element in the woundto improve the release of body fluid. For lancing skin with theskin-piercing element e.g. conventional spring type lancing units may beemployed. Further electrical drives for lancing as e.g. described in EP1101443 may be employed. The mentioned electrical drives alone orcombinations with other transport means may be employed for abovedescribed movements of the skin-piercing means.

In order to enhance sampling with the skin-piercing means vacuum may beemployed to withdraw body fluid. Such vacuum can be applied to the skinarea where skin-piercing is made or in case of a hollow sampling needlevacuum may be applied to the channel of the sampling needle.

The skin-piercing element may be transferred to the fluid receivingmeans to contact the skin-piercing element with the fluid receivingmeans by the above mentioned transport means. Additionally, theskin-piercing element may be transferred manually e.g. by the user, forexample by using a lancet inserted in a skin-piercing device to piercethe skin and collect the body fluid sample. It may then be moved to ameasurement instrument having a fluid receiving means inserted, and thecollection zone is brought into contact to the fluid receiving meanstransferring the body fluid sample.

Test zones are especially prone to deterioration by humidity. Thereforetest zones need to be sheltered in some way when stored. Theskin-piercing means of the present invention can be employed to pierce asealing of a sealed fluid receiving element. This is advantageous sinceadditional means or steps for unpacking or opening of a sealing can beavoided.

According to the invention it is possible that the skin-piercing elementis moved to the fluid receiving means, or that the fluid receiving meansis moved to the skin-piercing element, or that both elements are moved.

When a magazine with fluid receiving means is employed there further canbe the steps of exposing a specific fluid receiving means from thestored fluid receiving means to contact the skin-piercing element loadedwith sample fluid. When the specific fluid receiving means has beenevaluated another fluid receiving means may be exposed to contact samplefluid on a skin-piercing element. It is possible that the used fluidreceiving means is stored in the same magazine or in an additional wastemagazine, or that the fluid receiving means is directly disposed, e.g.manually.

An automated system according to above shuttle concept therefore has oneor more skin-piercing elements, a drive for driving a skin-piercingelement to pierce skin, and a transport means to bring the skin-piercingelement into contact with a fluid receiving means. The drive forpiercing and the transport means may be employed in the same drive unit.Transport means can comprise for example electrical actuation, springforce actuation, manual actuation, e.g. by pushing a slider and acombination of these means. In a manual system according to aboveshuttle concept skin-piercing element and the fluid receiving means arein separated units and the transport to contact each other may be donemanually, e.g. the user pricks the skin and collects the sample fluidwith the skin-piercing element and then moves the skin-piercing elementto the fluid receiving means, or vice versa, to contact the fluid samplewith the fluid receiving means.

Although it is preferable to move the skin-piercing element to the fluidreceiving means, it is also possible to transfer the fluid receivingmeans to the skin-piercing element, or to move both elements. Furtherthe systems may comprise a storage unit for multiple fluid receivingmeans. The systems further may comprise an exposing unit forsuccessively exposing fluid receiving means to receive fluid. Theskin-piercing element may contact the fluid receiving means and thefluid sample is transferred on the fluid receiving means to the testzone, or the skin-piercing element may contact the test zone and thefluid sample is directly transferred to the test zone.

Further a fluid receiving means may be employed that has no test zonebut a separate test zone is contacted with the fluid receiving means sothat finally the test zone is wetted with sample fluid.

The fluid receiving means is a structure that can take up fluid from acollection zone of the skin-piercing element. This uptake of fluid e.g.can be accomplished for example by an electrical potential appliedbetween fluid in the collection zone and the fluid receiving means. FIG.5 shows the concept of electrical triggering a contact of sample fluidwith the test zone. A skin-piercing element (14) having a collectionzone (9) is spaced from a fluid receiving means (10) by spacers (11). Ahigh electrical potential is applied between an electrode (12) being incontact with the body fluid sample in the collection zone (9) and secondelectrode (13) contacted to the fluid receiving means. This may causeeither fluid sample to move from the collection zone onto the test zoneor may cause a movement of the fluid receiving means in direction of thecollection zone. In both cases wetting of the test zone by sample fluidcan be triggered in a very short time frame by turning on the electricalpotential.

Preferably, the fluid receiving means has a higher capillarity than thecollection zone of the skin-piercing element so that during contactfluid is automatically taken up, i.e. the capillarity difference servesas contacting means. In this regard the fluid receiving means can bemade from a fleece or fabric material that has a high capillarity and ishydrophilic (at least in areas for fluid take-up). The fluid receivingmeans may have a particular region which comprises such material of highcapillarity or the whole area of the fluid receiving means can act asreceiving means for fluid from the fluid channel. The fluid receivingmeans may be a test zone in itself which can be covered with a fabric orwoven material or the fluid receiving means may be more complex andallows for pre-processing of sample fluid and/or transport of fluid to asensor/test zone. Pre-processing may comprise filtration of fluid sampleand/or a mixing with reagents. Alternatively or to support the capillaryforce as contacting means a mechanical force can be applied pressingcollection zone and receiving element together, or overpressure on theside of the collection zone and/or under pressure, e.g. vacuum, on thereceiving side may be applied. In particular at collection zonescomprising through holes overpressure on one end of the holes may beused to ensure that at least a portion of the sample leaves thecollection zone through the other end and contacts the fluid receivingmeans. Mechanical compressing means or ultrasound, (e.g. in sawtoothoperation), are also possible contacting means to transfer the fluidsample to the receiving means.

The fluid receiving means comprises a test zone with at least onechemistry layer that contains a reagent for detecting an analyte. Thereagent undergoes a detectable change due to reaction with the analyteto be detected. Typical reagents for detecting glucose are based forexample on glucose oxidase in conjunction with a chromogenic redoxsystem. Reagents are well known in the prior art for optical evaluationwhich form a colour with glucose from the body fluid. Furthermorereagents are also known from the field of blood sugar test strips whichallow electrochemical detection of analytes. The reagent mixtures thatare used are usually in a solid state and, due to their constituents(e.g. aluminium oxide, kieselguhr and such like), have such a highcapillarity that they can take up body fluid from the capillary channel.Since these detection systems are well-known from the prior art they arenot described in more detail herein but reference is made to U.S. Pat.No. 5,762,770 and U.S. Pat. No. 36,268.

A preferred embodiment of a body fluid collection system according tothe present invention additionally has a drive unit which, whenactivated, moves the skin-piercing element from a first into a secondposition such that it performs a lancing movement. Suitable drive unitsare well-known from the field of blood sampling systems. It can forexample contain a spring which is cocked by the user and when releaseddrives the skin-piercing element. A particularly advantageous drive unitis described in EP B 0 565 970.

Systems for body fluids analysis comprise a detection unit. If asensor/test zone containing reagent is used which changes colour orforms a colour when an analyte is present, the system can have anoptical detection unit comprising a light source and a detector todetect transmitted or reflected light. When electrochemical detection isemployed, the system has electrodes which contact the test zone or thefluid receiving means. For evaluation of raw signals the system can haveelectronic devices known in the prior art in order to determine theconcentration of analyte for example by measuring the so-called Cotrellcurrent (see e.g. U.S. Pat. No. 36,268).

With the skin-piercing element according to the present invention bodyfluid can be withdrawn while the protruding portion is inserted in theskin or the protruding portion can be retracted from the body afterpiercing and takes up body fluid that emerges on the body surface. Theproducing portion comprising the collection zone in the body during thecollection of the body fluid is preferred. A partial withdrawal in whichthe protruding portion remains in the body to collect body fluid isespecially suitable for sampling at the arm. This is due to the factthat small incisions on the arm close very rapidly such that no fluid oronly very small amounts of fluid emerge after piercing. On the otherhand the sensitivity to pain is much less pronounced on the arm ascompared for example to the finger and thus when the protruding portionremains in the body this is not felt to be painful.

Furthermore a withdrawal process can be carried out with the samplingdevice according to the invention which is a combination of thepreviously mentioned processes. In this combined process piercing iscarried out firstly, the protruding portion may be pulled back over apart of the piercing path and to allowed to reside there for acollection period. Depending on the circumstances it may be possible toremove residual blood almost completely so that no blood is seen by theuser.

A further decisive factor which is important for an efficient uptake ofbody fluid is the wettability of the collection zone. When capillarystructures made of silicon are used, these are usually adequatelywettable due to a silicon oxide layer on the surface. If metals are usedfor the capillary structure, these are often relatively difficult towet. This can be counteracted by a number of different hydrophilisationmeasures such as silication of the surface. The wettability is usuallyadequate when the liquid in the capillaries has a concave meniscus whichis the case when the wetting angle is less than 90°.

In a preferred embodiment of a body fluid collection system the volumeof the fluid sample is very small, i.e. less than 0.5 μl, preferably 3to 10 mL. Such a small volume can be collected very fast, e.g. usingvery small holes of for example 20 μm in diameter generating highcapillary forces for rapid filling. The time to receive sufficientamount of body fluid sample can be less than 0.1 s, e.g. 1 to 10 ms.Accordingly the interaction time between the skin-piercing element andthe body while the skin-piercing element remains in the body andsufficient amount of body fluid sample is received may be less than 0.5s, e.g. about 10 ms. Preferably the body fluid sample is collected inthe body so that virtually no blood is visible on the skin. According tothe invention the geometry of the collection zone and hence the bodyfluid volume that is collected is defined precisely, e.g. the risk ofover- or underdosing of the fluid receiving means is significantlyreduced.

Using a sampling device according to the invention the receiving of thebody fluid sample may take less than 0.1 s, preferably 10 to 15 ms.

Advantageously an expression means to express sample fluid from a bodyportion may be employed in the present invention. An expression meansmay be a specially formed finger cone (15) to be used to improve samplecollection as described in FIG. 6. It shows an example of the operationand action of a finger cone (15) according to U.S. Pat. No. 6,589,260.As shown in FIGS. 6A and 6B a finger tip is pressed by the user onto thefinger cone such that the finger cone is pressed together and the innerwidth (16) of the finger cone is reduced. As a result a part of thefinger tip is squeezed and the internal pressure in this region (17) isincreased. This design improves body fluid sampling in the collectionzone and minimizes the body fluid leaking from the body. The inner width(16) should ideally be in the range of 8 to 11 mm in order to besuitable for large adult fingers as well as children's fingers.

A body fluid sampling system with an automatic transfer of thecollection zone to the fluid receiving means according to the presentinvention is a fast one-step operation system which is easy to use evenfor elder, disabled or blind users. Due to the small sample volume thatis collected the risk for contaminating the system components,especially the measurement instrument, is reduced promoting hygienicdisposal of used fluid receiving means.

The high mass of the skin-piercing element compared to the very lowfluid sample volume makes it easy to keep the temperature variation ofthe sample small, preferably below 10° C., e.g. by heating theskin-piercing element to a temperature of 20° C. to 40° C., preferably30° C. For precise testing it is also preferred to provide a constanttemperature in the testing region which is in the range between 20° C.to 40° C.

Advantageously skin-piercing elements and/or fluid receiving means maybe provided in magazines. A possible embodiment may comprise, forexample, a skin-piercing device with a magazine for skin-piercingelements and/or a fluid receiving means magazine as separated unit ore.g. integrated in the measurement instrument.

A preferred embodiment of lancets as skin-piercing elements and teststrips as fluid receiving means arranged in a magazine according to thepresent invention is shown in FIGS. 7-11. FIGS. 7 and 8 describe amagazine (21) for skin piercing elements and a concentric outer teststrip drum magazine (22) with separate chambers for each fluid receivingmeans (23). Each chamber is sealed by a foil and each element has anexternal grip to which a driving mechanism of the instrument can beconnected to move the element out of the magazine and back into themagazine. Tearable foils (25) seal the chambers. The skin-piercingelement and the fluid receiving means are each mounted on respectivesliders (27) guiding the movement of the element. FIG. 9 shows a lancet(24) with a collecting zone being moved forward to penetrate skin andcollect sample. During this movement the respective sealing foil isbroken. FIG. 10 shows how the skin piercing element (24) is brought to acontacting position, e.g. by moving it back. The fluid receiving means(23) is also moved to the contacting position, e.g. by moving itforward. In a preferred embodiment the fluid receiving means is bendwhen stored in the cavity and comes to a position as shown in FIG. 10when being moved out of it. By this the fluid receiving means comes intocontact with the fluid collection zone. Alternatively fluid receivingmeans and skin-piercing element are pushing together by suitableactuation means. When the fluid receiving means is pressed against thecollection zone of the element (24) the sample from the skin piercingelement is transferred to the fluid receiving means to wet a test zonewith sample. The test zone is for example read optically from thebackside to confirm sample transfer and to determine glucoseconcentration. FIG. 11 shows how after the test is completed the usedskin piercing element (24) and fluid receiving means (23) are drawn backinto their respective drum chambers for storage.

In a fluid sampling system according to the invention preferably thecollection direction of the body fluid sample flow entering thecollection zone is not parallel, but preferably perpendicular, to themain actuation/lancing direction of the skin-piercing element.

A system according to the invention provides a disposable skin-piercingelement and fluid receiving means avoiding direct contact of reagentchemistry and the body.

A skin piercing element may be made hydrophilic to improve the receptionof body fluid. Hydrophilization may be conducted on the whole element oron selected regions.

In a preferred system according to the invention the body fluid samplecollected in the collection zone is moved onto the fluid receiving meanswithout using further body fluid as transfer means, i.e. the sample istransferred by mechanical, preferable electrical or manual means and notby fluid means. This method has the advantage that the body fluid can betransferred over a long distance if needed without increasing the deadvolume, and the sample can be delivered to a small distinct spot, i.e.the test zone. Consequently the fluid receiving means size can bereduced.

FIG. 12 shows another preferred embodiment of a skin-piercing elementcomprising a round, solid lancet (4) with a groove or recess (31), e.g.milled or etched, to form a collection zone (2).

FIG. 13 shows a skin-piercing element (14) which has a collection zone(9) which runs in an elongated portion of the skin-piercing element.This portion is connected to a holder (32) in form of a frame. Theelongated portion has a protruding portion (33) which protrudes from theholder portion (32). At the front end of the protruding portion asharpened tip (3) is located. The sharpened tip (3) enables penetrationof the skin surface during pricking with the skin-piercing element. Thecollection zone (9) is located in the front end region of the protrudingportion. The collection zone is an open capillary channel which permitsbody fluid which contacts the channel in the region of the protrudingportion to move into the moveable portion of the collection zone (34) bymeans of capillary action. As depicted in FIG. 13 protruding portion(33), moveable portion (34) and frame portion (32) of the skin-piercingelement (14) are formed integrally. The skin-piercing element (14) canbe made by etching processes. As well known in silicon manufacturingprocesses a wafer of silicon material can be etched to provide devicescomprising tips and capillary channels. For mass production it ishowever advantageous to produce the skin-piercing elements by etching ofthin metal plates. It is particularly advantageous that the sharpenedtip (3) of the protruding portion (33) can be formed during the etchingprocess as well so as to avoid separate grinding steps. As can be seenfrom FIG. 13 there is no reagent or sensor contacting the fluid channelwhich would receive body fluid immediately after the collection zone hasbeen filled with sample fluid. The present invention proposes to locatea test zone or sensor separately on a fluid receiving means.

FIG. 14 shows the skin-piercing element (14) of FIG. 13 together with afluid receiving means (10) including a test zone (35). The fluidreceiving means (10) is shown schematically. The fluid receiving means(10) is located on the upper side of the skin-piercing element (14) onwhich side the fluid channel (9) is open to the environment. The fluidreceiving means (10) is, however, initially spaced from the collectionzone (9) so that sample fluid within the collection zone does notcontact the fluid receiving means. Therefore no fluid transfer from thecollection zone onto the fluid receiving means occurs in this geometryof the fluid sampling device. In the depicted embodiment the fluidreceiving means essentially consists of a holding structure (11) whichprovides proper orientation and spacing of the fluid receiving meansrelative to the skin-piercing element and the test zone (35). In thedepicted embodiment the test zone includes a reagent which produces anoptical signal based on the concentration of analyte in the body fluid.Due to the incorporation of porous materials as e.g. kieselghur ortitanium dioxide, the reagent already has high capillarity that sucksfluid from capillary channel (9). The reagent is applied to a carriersurface. After fluid has been received in the collection zone and hasfilled the moveable section (34) the body fluid sampling device isprimed for measurement. By means of mechanical actuation the moveablesection (34) can be bent in direction of the sensor (35) so that bodyfluid located in the collection zone (9) contacts the test zone (35) andwets the reagent. This mode of contacting the sensor with sample fluidhas several advantages over the prior art devices.

A first advantage over the prior art is that measurement can beinitiated at a specific point in time. This means that the time betweenwetting of the test zone and measurement of the final signal can bechosen at will. The time period, however, is shorter than the dryingtime of blood in the capillary. Knowing or controlling the time ofreaction improves accuracy of the measurement. Further a signal can bemeasured beginning directly after wetting which allows to monitorreaction kinetics. Evaluation of this early signals can be used toimprove accuracy of the measurement result as well.

FIG. 15 describes a body fluid testing device that contains a pluralityof test zones located on a test media cassette (10) serving as fluidreceiving means which allows multiple testing (see e.g. EP 1 424 040).The cassette (10) includes a supply portion that stores anuncontaminated section (41) of the test media tape. A storage portionfor storing a contaminated section (42) of the test media tape isfurther employed. The testing device is a handheld device that can beconveniently handled by a user. The test media tape (10) may be part ofthe testing device so that the whole device is discarded when the testmedia tape is used up or the test media tape may be arranged in adisposable cassette which is received in the testing device. The bodyfluid will be applied on a sensing region (43) which is positionedbetween the supply portion (41) and the storage portion (42) to sense ananalyte of the body fluid collected on the test media cassette. Thetesting device further comprises a pricking unit (skin-piercing element,14) for pricking a body portion. The pricking unit advantageously isarranged close to the sensing region.

FIG. 16 shows an embodiment of the present invention where a skinpiercing element (1′) including a collection zone (2′) and a fluidreceiving means (10′) are connected via a hinge (50). FIG. 16 a) shows aconfiguration suitable for lancing skin and sampling body fluid with thecollection zone (2′). The collection zone e.g. can be chosen accordingto the embodiments as described for FIGS. 1 to 4. When fluid has beensampled the skin-piercing element is withdrawn and is folded so that thecollection zone (2′) contacts a test zone (35′) on the receiving means.Measurement can be made in this folded configuration from beneath.However, it is also possible to unfold the device and to measure thecolour of wetted portion (51) on the test zone (35′) from the upper sideas depicted in FIG. 16 c).

Alternatively to folding an integrated sampling and testing deviceaccording to FIG. 16 it is also possible to rotate skin-piercing elementand sample receiving means in a plane to contact sample on the skinpiercing element with a test zone.

FIG. 17 depicts a further embodiment to transfer sample from a skinpiercing element (1″) onto a test zone (35″). FIG. 17 a shows a skinpiercing element that already has sampled fluid and has been retractedinto a housing. Two parts (60, 60′) are provided which press a rubberseal (61) onto the skin-piercing element so that a region which holdssampled fluid is sealed from one side. Application of further pressuresqueezes the rubber seal and fluid from the skin piercing element istransferred onto test zone (35″) lying underneath. Instead or inaddition to transfer fluid by contacting, fluid transfer is made viapneumatic actuation in this embodiment. Compared to devices according toe.g. WO 01/72220 where pneumatic actuation is employed too, here arelative movement of the skin-piercing element and the fluid receivingmeans (10″) has been employed before the pneumatic actuation takesplace. As described earlier on this allows to separate the lancingportion from the testing portion and hence sterilization can be madewithout destroying the test chemistry.

FIG. 17 further shows that sample fluid from holes in the collectionzone of the skin-piercing element is transferred to opposing areas ofthe testing zone. The geometric pattern of the holes in the collectionzone results in a similar pattern on the test zone. When conventionaldry chemistries are employed the wetted areas on the test zone areinitially roughly as large as the diameter of the holes in thecollection zone and fluid moves vertically. It is preferred to evaluatethe analyte dependent reaction from the side opposite to sampleapplication to separate fluid transfer from the optics. Accordingly itis required to achieve complete wetting through the thickness of thetest zone so that even the lowermost portion of the test zone reacts.Sufficient wetting e.g. is achieved if the thickness of the test zone issmaller than the depth of the holes in the collection zone. Preferablythe thickness of the fluid receiving zone of the test zone is 10 to 80%of the depth of the holes in the collection zone. This means that verysmall thin skin-piercing elements can be employed as will become clearerby the following example. Today it is well feasible to produce drychemistries having a liquid receiving structure with a thickness in theorder of 10 to 50 micrometers only. To assure proper wetting the depthof the holes in the skin-piercing element only need to be in the orderof 50 to 500 micrometers to collect sufficient fluid volumes even if thecollecting holes are not completely filled. This in turn means thatskin-piercing elements of this thickness or slightly more may beemployed. Therefore it is preferred if the skin-piercing element has athickness below 500, even more preferred below 250 micrometers.Skin-piercing means of the present invention therefore can be maderoughly as thin as today's lancets which do not sample fluid. Althoughthe sampled volume of collected fluid is in the nanoliter range only,reliable measurements can be achieved due to the availability ofsuitably thin dry chemistry test zones.

FIG. 18 shows a skin piercing element having two parts (70, 70′) whichcan be moved relative to one another. In FIG. 18 a the parts (70, 70′)are aligned to form a capillary channel into which sample is received.The filled device (FIG. 18 b) is rearranged as shown in FIG. 18 c. Atone end of the channel the parts are moved apart and hence the sample isconcentrated in the region (71) where the parts are still closetogether.

FIG. 19 shows an array of sealed fluid receiving means (83) which aresealed against the environment by a sealing foil (88) (e.g. an aluminalaminate). The skin-piercing means (84) is located in a handheld device(80). The skin-piercing means as depicted is already filled with sampleand is moved to the array of fluid receiving means. The skin-piercingelement itself or as depicted a separate tip (85) may be employed topierce the sealing foil. The tip of the skin-piercing element is thencontacted with a test zone beneath the broken sealing foil to transfersample fluid. Measurement of analyte concentration can be made from theunderside with an optics (86) as shown schematically. To allow opticalinspection the test zone is located on a transparent support (87).

Preferred features of the current invention are listed below:

Body fluid sampling device comprising a skin-piercing element having acollection zone for receiving body fluid and a fluid receiving meanscomprising a test zone and being spaced from said collection zone sothat fluid in said collection zone will not contact the fluid receivingmeans, wherein said skin-piercing element has two or more collectionzones.

Body fluid sampling device according to the invention, wherein thecollection zone comprises through holes or blind holes.

Body fluid sampling device according to the invention, wherein thecollection zone comprises through a rough surface or a recess to receivethe body fluid.

Body fluid sampling device according to the invention, wherein thevolume of the body fluid received by the sampling device is 3 to 10 nL.

Body fluid sampling device according to the invention, wherein the timeof the skin-piercing element remaining in the body to receive the bodyfluid sample is 10 msec.

Body fluid sampling device according to the invention, wherein the timeto receive a sufficient amount of the body fluid sample is less than 0.1sec, preferably 1 to 10 msec.

System for body fluid analysis comprising a skin-piercing element with acollection zone for receiving body fluid, wherein at least a portion ofsaid collection zone is open to the environment and a fluid receivingmeans remote from said collection zone so that fluid in said pathwaywill not contact the fluid receiving means, said fluid receiving meanscomprising a test zone, wherein said system comprises a meter with adetection unit for receiving signals from said test zone to determinethe presence and/or concentration of analyte.

System according to the invention, wherein the meter includes a holderin which the fluid receiving means is received and signal transmissionfrom the test zone to the detector is enabled.

System according to the invention, wherein said meter has a processingunit that receives a signal indicating that the contacting means hascontacted the collection zone with the fluid receiving means or thatsample fluid has reached the test zone.

System according to the invention, further comprising an exposing unitfor successively exposing fluid receiving means from said magazine toreceive fluid.

Method for determining an analyte concentration in body fluid comprisingthe steps of:

-   -   a) receiving body fluid in a collection zone of a skin-piercing        element,    -   b) contacting the collection zone of the skin-piercing element        with the fluid receiving means so that body fluid reaches a test        zone on the fluid receiving means,    -   c) receiving signals from said test zone which are        characteristic for an analyte concentration    -   d) processing said signals to determine the analyte        concentration,        wherein a time period beginning with step b) is monitored and        determination of analyte concentration is initiated based on the        time passed.

Method according to the invention, wherein step b) initiates amonitoring of signals and the change of signal over time is employed todetermine a point in time for concentration determination.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly the preferred embodiment has been shown and described and that allchanges, equivalents, and modifications that come within the spirit ofthe inventions defined by following claims are desired to be protected.

1. Body fluid sampling device, comprising: a skin-piercing elementhaving a collection zone for receiving body fluid, wherein thecollection zone comprises 3 or more holes in which the received bodyfluid is collected.
 2. Device according to claim 1, wherein at least aportion of said collection zone is open to the environment.
 3. Deviceaccording to claim 1, wherein the collection zone comprises a poroussurface to receive the body fluid.
 4. Device according to claim 1,wherein the volume of the body fluid received by the sampling device is0.5 μL (microliters) or less.
 5. Device according to claim 1, whereinthe thickness of the skin-piercing element is below 500 μm(micrometers).
 6. Device according to claim 5, wherein the thickness ofthe skin-piercing element is below 250 μm (micrometers).
 7. Deviceaccording to claim 1, wherein the collection zone comprises 50 to 100holes.
 8. System for sample analysis with a device according to claim 1,further comprising: a fluid receiving means with a test zone, whereinthe thickness of the test zone is 10 to 80% of the depth of the holes inthe fluid receiving zone of the skin-piercing element.
 9. An apparatus,comprising: a lancet adapted to penetrate the skin surface and obtain asample of body fluid, the lancet including a plurality of holes forminga collection zone, wherein the diameter of each hole is 0.01 mm(millimeters) to 0.5 mm (millimeters).
 10. The apparatus of claim 9wherein the diameter of each hole is 20 μm (micrometers).
 11. Theapparatus of claim 9 wherein the depth of each hole is 50 to 500 μm(micrometers).
 12. The apparatus of claim 9 wherein the plurality ofholes includes 50 to 100 holes.
 13. The apparatus of claim 9 wherein thesample volume of the collection zone is less than 0.5 μL (microliters).14. The apparatus of claim 9 wherein the sample volume of the collectionzone is 3 to 10 nL (nanoliters).
 15. The apparatus of claim 9 whereinthe holes extend through the lancet.
 16. The apparatus of claim 9wherein the holes do not extend through the lancet.
 17. An apparatus,comprising: a lancet adapted to penetrate a skin surface to obtain asample of body fluid, the lancet including a collection zone adapted tohold a sample of bodily fluid as the lancet is withdrawn from the skin.18. The apparatus of claim 17 wherein the collection zone is porous. 19.The apparatus of claim 17 wherein the collection zone is a roughenedarea on the surface of the lancet.
 20. The apparatus of claim 17 whereinthe collection zone includes a plurality of holes.
 21. The apparatus ofclaim 17 wherein the collection zone includes 50 to 100 holes.
 22. Theapparatus of claim 17 wherein the collection zone includes a pluralityof holes with a diameter of 0.01 mm (millimeters) to 0.5 mm(millimeters).
 23. The apparatus of claim 17 wherein the collection zoneincludes a plurality of holes extending through the lancet.
 24. Theapparatus of claim 17 wherein the collection zone includes a pluralityof holes that do not extend through the lancet.
 25. The apparatus ofclaim 24 wherein the depth of the holes are 50 to 500 μm (micrometers).26. The apparatus of claim 17 wherein the sample volume of thecollection zone is 3 to 10 nL (nanoliters).
 27. The apparatus of claim17 wherein the collection zone is configured and adapted to fill with asample of body fluid in less than 0.1 seconds.
 28. The apparatus ofclaim 17 wherein the collection zone is configured and adapted to fillwith a sample of body fluid in 1 to 10 ms (milliseconds).